New study identifies genetic markers that could guide emerging prostate cancer treatments

UT MD Anderson Research News July 02, 2026

• Ferroptosis is a type of cell death that has emerged as a promising avenue to target cancers that are resistant to current therapies
• This study identified how two common genetic alterations have opposing influences over susceptibility to ferroptosis
• The findings identify SPOP mutations and CHD1 deletions as potential biomarkers that could help guide future patient selection for ferroptosis-targeting therapies

A new study from researchers at The University of Texas MD Anderson Cancer Center has identified genetic factors that determine whether prostate cancers are susceptible to a type of cell death known as ferroptosis. These findings, published in Nature Communications, could help guide treatment strategies for patients whose tumors do not respond to current treatment options. 

The study was led by Di Zhao, Ph.D., associate professor, and Boyi Gan, Ph.D., professor, both of Experimental Radiation Oncology. 

“Prostate cancer is such a genetically diverse cancer that there are many possible treatment options, so getting patients on the right treatment as quickly as possible is crucially important,” Zhao said. “The two genetic findings in this study could help identify some patients that are more likely to respond, as well as some patients that are significantly less likely.”

What are the key genetic findings of this study in prostate cancer? 

Two common genetic alterations in prostate cancers are SPOP mutations and CHD1 deletions. 

SPOP is a gene that is a known tumor suppressor, meaning it normally acts to stop tumor development, but mutations can cause a disruption in this role. This study found that one of the downstream effects of SPOP disruption is an increase in an enzyme known as ACSL4 that loads fatty acids into cell membranes, which is what ferroptosis-inducing therapies target. As a result, SPOP-mutant prostate cancers are more vulnerable to ferroptosis. 

CHD1 deletions have the opposite effect, causing a drop in ACSL4 levels and reducing how vulnerable the cancer cells are to ferroptosis. In the study, using a statin therapy already approved to lower cholesterol levels helped restore ACSL4 levels, sensitizing these tumors to ferroptosis in preclinical models. 

How could these findings impact treatment for prostate cancer? 

A common ferroptosis-inducing strategy currently being investigated in preclinical and early-phase studies is a class of therapies known as GPX4 inhibitors. These work by blocking an enzyme that prevents the types of fatty acid buildup that leads to ferroptosis. 

These findings suggest that SPOP mutations and CHD1 deletions could serve as biomarkers to help identify which prostate cancers are more likely to respond to GPX4 inhibitors currently being evaluated. The research also went one step further in identifying why some cancers don’t respond – because they have CHD1 deletions – and identified a potential strategy to overcome that resistance. 

“Ferroptosis is a promising strategy for treating therapy-resistant cancers, but we still need to understand which tumors are most likely to benefit,” Zhao said. “By identifying SPOP mutations and CHD1 deletions as key determinants of ferroptosis sensitivity, our findings provide a foundation for developing more precise and effective ferroptosis-based therapies.”

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 This study was supported by the National Institutes of Health’s (NIH) National Cancer Institute (NCI), Department of Defense (DoD) Congressionally Directed Medical Research Programs (CDMRP), Prostate Cancer Foundation, the Cancer Prevention & Research Institute of Texas (CPRIT), and the Collaborative Accelerator for Transformative Research Endeavors grant from UT MD Anderson and The University of Texas at Austin. A full list of collaborating authors and their disclosures can be found with the full paper in Nature Communications.